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Title: Dosage compensation can buffer copy-number variation in wild yeast

Journal Article · · eLife

Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10–30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
Grant/Contract Number:
FC02-07ER64494; R01GM083989; R21HG006568
OSTI ID:
1227971
Alternate ID(s):
OSTI ID: 1227972; OSTI ID: 1628830
Journal Information:
eLife, Vol. 4; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 87 works
Citation information provided by
Web of Science

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Identification of Aneuploidy-Tolerating Mutations journal October 2010
“Changing by doubling”, the impact of Whole Genome Duplications in the evolution of eukaryotes journal February 2009
Genome-wide expression studies in Autism spectrum disorder, Rett syndrome, and Down syndrome journal January 2012
Redundancy and rewiring of genetic networks following genome-wide duplication events journal April 2012
Expression divergence between duplicate genes journal November 2005
Widespread aneuploidy revealed by DNA microarray expression profiling journal July 2000
A general lack of compensation for gene dosage in yeast journal January 2010
Phosphorylation network rewiring by gene duplication journal January 2011
A dynamic model of proteome changes reveals new roles for transcript alteration in yeast journal January 2011
Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast journal October 2010
Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy journal January 2012
Duplicate genes increase gene expression diversity within and between species journal May 2004
Inventory control: cytochrome c oxidase assembly regulates mitochondrial translation journal December 2010
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Eucaryotic genome evolution through the spontaneous duplication of large chromosomal segments journal December 2003
Rapid evolution of expression and regulatory divergences after yeast gene duplication journal January 2005
The evolutionary dynamics of the Saccharomyces cerevisiae protein interaction network after duplication journal January 2008
Transcriptional consequences of aneuploidy journal July 2012
Chromosomal duplication is a transient evolutionary solution to stress journal November 2012
Aneuploidy underlies a multicellular phenotypic switch journal June 2013
Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae journal November 2002
Natural Gene-Expression Variation in Down Syndrome Modulates the Outcome of Gene-Dosage Imbalance journal August 2007
Detecting differential gene expression with a semiparametric hierarchical mixture method journal April 2004
Copy-Number Variation: The Balance between Gene Dosage and Expression in Drosophila melanogaster journal January 2011
Growth Rates Made Easy journal October 2013
Yeast mitochondrial NAD + -dependent isocitrate dehydrogenase is an RNA-binding protein journal January 1993
Up-to-date catalogues of yeast protein complexes journal December 2008
Local climatic adaptation in a widespread microorganism journal February 2014
Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments journal February 2012
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Genome and gene duplications and gene expression divergence: a view from plants: Gene duplication and expression divergence journal May 2012
Aneuploidy and Isochromosome Formation in Drug-Resistant Candida albicans journal July 2006
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast journal August 2007
New Insights into the Troubles of Aneuploidy journal November 2012
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Comparative genomics of wild type yeast strains unveils important genome diversity journal January 2008
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Unisexual and Heterosexual Meiotic Reproduction Generate Aneuploidy and Phenotypic Diversity De Novo in the Yeast Cryptococcus neoformans journal September 2013
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Incipient Balancing Selection through Adaptive Loss of Aquaporins in Natural Saccharomyces cerevisiae Populations journal April 2010
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Pathway connectivity and signaling coordination in the yeast stress‐activated signaling network journal November 2014
Natural Variation in the Yeast Glucose-Signaling Network Reveals a New Role for the Mig3p Transcription Factor journal December 2012

Cited By (49)

When and why does sex chromosome dosage compensation evolve?: Evolution of sex chromosome dosage compensation journal January 2017
Haploid yeast cells undergo a reversible phenotypic switch associated with chromosome II copy number journal December 2016
Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells text January 2017
Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance journal February 2018
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster. text January 2016
Ploidy dynamics and evolvability in fungi journal December 2016
Genome evolution across 1,011 Saccharomyces cerevisiae isolates journal April 2018
Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes posted_content December 2017
Complex networks of miRNA-transcription factors mediate gene dosage compensation in aneuploid cancer posted_content February 2020
Natural Variation in the Multidrug Efflux Pump SGE1 Underlies Ionic Liquid Tolerance in Yeast journal July 2018
Translational compensation of gene copy number alterations by aneuploidy in Drosophila melanogaster journal February 2017
Fermentation innovation through complex hybridization of wild and domesticated yeasts journal October 2019
Evolution of new enzymes by gene duplication and divergence journal April 2020
Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells journal October 2017
Industrial Relevance of Chromosomal Copy Number Variation in Saccharomyces Yeasts journal March 2017
Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker’s Yeast journal October 2018
Homoeologous exchanges cause extensive dosage-dependent gene expression changes in an allopolyploid crop journal October 2017
A unique ecological niche fosters hybridization of oak-tree and vineyard isolates of Saccharomyces cerevisiae journal November 2015
YEASTRACT: an upgraded database for the analysis of transcription regulatory networks in Saccharomyces cerevisiae journal September 2017
Single-cell RNA sequencing reveals the impact of chromosomal instability on glioblastoma cancer stem cells journal May 2019
The diverse consequences of aneuploidy journal January 2019
Aneuploidy Enables Cross-Adaptation to Unrelated Drugs journal April 2019
Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression journal May 2017
Molecular signatures of aneuploidy-driven adaptive evolution journal January 2020
Whole Genome Analysis of 132 Clinical Saccharomyces cerevisiae Strains Reveals Extensive Ploidy Variation journal June 2016
Population genomics of yeasts: towards a comprehensive view across a broad evolutionary scale: Insights into yeast population genomics journal January 2016
A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation journal October 2019
Recombining Your Way Out of Trouble: The Genetic Architecture of Hybrid Fitness under Environmental Stress journal September 2019
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster journal September 2016
Aneuploidy in yeast: Segregation error or adaptation mechanism? journal August 2019
Genome plasticity in Candida albicans is driven by long repeat sequences journal June 2019
The genetic basis of aneuploidy tolerance in wild yeast journal January 2020
Molecular signatures of aneuploidy-driven adaptive evolution journal January 2020
Genome evolution across 1,011 Saccharomyces cerevisiae isolates journal April 2018
Aneuploidy Enables Cross-Adaptation to Unrelated Drugs journal April 2019
Recombining Your Way Out of Trouble: The Genetic Architecture of Hybrid Fitness under Environmental Stress journal September 2019
Asymmetric cell division requires specific mechanisms for adjusting global transcription journal October 2017
Complex networks of miRNA-transcription factors mediate gene dosage compensation in aneuploid cancer posted_content February 2020
Single-cell RNA sequencing reveals the impact of chromosomal instability on glioblastoma cancer stem cells journal May 2019
NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins journal October 2017
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster journal September 2016
Massive Amplification at an Unselected Locus Accompanies Complex Chromosomal Rearrangements in Yeast journal May 2016
Dissecting Gene Expression Changes Accompanying a Ploidy-Based Phenotypic Switch journal November 2016
Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation journal August 2016
A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation journal October 2019
No current evidence for widespread dosage compensation in S. cerevisiae journal March 2016
Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution journal August 2016
Genome plasticity in Candida albicans is driven by long repeat sequences journal June 2019
The genetic basis of aneuploidy tolerance in wild yeast journal January 2020

Figures / Tables (12)